title: Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis.
abstract: Nanoscaled drug-loaded carriers are of particular interest for efficient tumor therapy as numerous studies have shown improved targeting and efficacy. Nevertheless, most of these studies have been performed against allograft and xenograft tumor models, which have altered microenvironment features affecting the accumulation and penetration of nanocarriers. Conversely, the evaluation of nanocarriers on genetically engineered mice, which can gradually develop clinically relevant tumors, permits the validation of their design under normal processes of immunity, angiogenesis, and inflammation. Therefore, considering the poor prognosis of pancreatic cancer, we used the elastase 1-promoted luciferase and Simian virus 40 T and t antigens transgenic mice, which develop spontaneous bioluminescent pancreatic carcinoma, and showed that long circulating micellar nanocarriers, incorporating the parent complex of oxaliplatin, inhibited the tumor growth as a result of their efficient accumulation and penetration in the tumors. The reduction of the photon flux from the endogenous tumor by the micelles correlated with the decrease of serum carbohydrate-associated antigen 19-9 marker. Micelles also reduced the incidence of metastasis and ascites, extending the survival of the transgenic mice.
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.forename: Mami
authors.initials: M
authors.lastname: Murakami
authors.forename: Hironori
authors.initials: H
authors.lastname: Hojo
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Terada
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.forename: Ung-il
authors.initials: UI
authors.lastname: Chung
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers; D051379:Mice; D008823:Micelles; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000517:prevention & control / Q000556:secondary*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles
keywords: (1,2-diaminocyclohexane)platinum(II); chemotherapy; drug delivery